Journal of Experimental Pharmacology最新文献

Introduction: The potato (Solanum tuberosum L.) is a short-lived tuber plant with a round to oval shape and varying colors, depending on the variety. It is known that only the inside of the potato is used, while the peel is generally discarded. However, recent studies have shown that potato peels contain many health-beneficial compounds.

Purpose: This study aimed to investigate the compounds present in potato peels and their in vitro activities.

Methods: A scoping review following the PRISMA guidelines was conducted. The selection process involved identifying articles of in vitro research published within the last 10 years (2012-2022). Electronic searches were conducted using the portals Scopus, ScienceDirect, EBSCOhost, and Portal Garuda by using the keywords "potato" or "Solanum tuberosum" and "peel" or "skin". The search was limited to articles in English with full text availability.

Results: The screening process resulted in a total of 4773 articles from the four search engines; 14 articles were obtained that met the requirements for the review, most of which use extract preparations in their research. Extracts of flavonoids, phenols, and glycoalkaloids are the most frequently studied compounds, and their antioxidant and anti-inflammatory activity have undergone extensive research.

Conclusion: The potential compounds contained in potato peels, including flavonoids, phenols, and glycoalkaloids, are highly abundant and offer numerous benefits. Provides opportunities for further research to prove the potential pathway activity of the compound. These compounds have been the subject of extensive research, suggesting their significance in the context of health and nutrition.

Purpose: To explore the potential therapeutic effects of Physalis angulata L. (Ciplukan) extract on lung fibrosis resolution in a Bleomycin-induced mouse model, researchers conducted a comprehensive study. The study focused on key genes associated with fibrosis progression, including Nox4, Mmp8, Klf4, and FAS, and assessed their mRNA expression levels following the administration of Ciplukan extract.

Methods: A Bleomycin-induced mice model was divided into seven groups to investigate the effects of ciplukan extract on fibrosis-related gene expressions. Mice were induced with subcutaneously injected Bleomycin to generate lung fibrosis and given different doses of the Ciplukan extract for four weeks. Lung fibrosis mRNA expression was analyzed by semi-quantitative PCR for Nox4, Klf4, Mmp8, and FAS.

Results: The administration of ciplukan extract resulted in a significant decrease in mRNA expression of Nox4 with p-value=0.000, Mmp8 with p-value =0.002, and Klf4 with p-value =0.007, indicating potential antifibrotic effects. However, FAS expression remained unchanged (p-value=0.127).

Conclusion: Ciplukan extract exhibited promising effects on fibrosis-related gene expressions, particularly Nox4, Mmp8, and Klf4. This study suggests that the extract has the potential to intervene in fibrosis progression, offering a potential avenue for therapeutic strategies.

Purpose: To assess the permeability of the test item (a combination of curcumin and piperine) and a reference item (dried and crushed turmeric rhizomes) using a combination of Caco-2 cell monolayer permeability assay and liquid chromatography-tandem mass spectrometry.

Methodology: In the Caco-2 cell assay, a transport buffer was prepared, and stock solutions of test and reference items were made. Caco-2 cells were cultured on transwell plates. Permeability assays were conducted for 2 and 6 hours, followed by post-experiment testing for assessing the monolayer integrity. LC-MS/MS (Liquid Chromatography with tandem mass spectrometry) analysis was performed to calculate apparent permeability of each item.

Results: The test item was undetectable at the end of 2 hours of permeability assay. Further, after 6 hours of permeability assay, the permeability of both test and reference item was found to be low.

Conclusion: The results showed that the curcumin and piperine combination had low permeability of curcumin in vitro as compared to the dried and crushed turmeric rhizomes. This could predict the low bioavailability of curcumin in vivo when co-administered with piperine.

Background: Viloxazine ER (viloxazine extended-release capsules; Qelbree^®), a nonstimulant attention-deficit/hyperactivity disorder (ADHD) treatment, has known activity as a norepinephrine (NE) transporter (NET) inhibitor. In vitro studies have also shown direct pharmacological effects on specific serotonin (5-HT) receptors, but not on the serotonin transporter (SERT). An in vivo microdialysis study in rats showed viloxazine (50 mg/kg i.p.) increased extracellular 5-HT, NE, and dopamine (DA) in the prefrontal cortex (PFC), a key brain region in ADHD pathology. This study evaluated whether these effects occur at clinically relevant concentrations.

Methods: Microdialysis experiments were conducted in freely-moving, Sprague-Dawley rats (males, 8 weeks). Viloxazine (1, 3, 10, 30 mg/kg) was administered intraperitoneally to establish the dose range in rats at which viloxazine plasma concentrations aligned with those of individuals with ADHD administered therapeutic doses of viloxazine ER. Concentrations of unbound viloxazine, NE, 5-HT, DA, and NE and 5-HT metabolites (3,5-dihydroxyphenylglycol [DHPG] and 5-hydroxyindoleacetic acid [5-HIAA]) were measured in PFC interstitial fluid. After identifying a therapeutically relevant dose (30 mg/kg), the experiment was repeated using 30 and 50 mg/kg viloxazine (as 50 mg/kg increased NE, 5-HT, and DA in prior studies).

Results: Viloxazine unbound (free drug) plasma concentrations in rats at 30 mg/kg were comparable to free drug concentrations in individuals with ADHD taking clinically effective doses (based on validated population PK models). Viloxazine 30 mg/kg significantly increased extracellular NE, 5-HT, and DA PFC levels compared to vehicle. Concomitant decreases in DHPG, but not 5-HIAA, support the inhibitory effect of viloxazine on NET but not SERT.

Conclusion: At clinically relevant concentrations, viloxazine increases PFC NE, DA, and 5-HT. Prefrontal augmentation of 5-HT does not appear to result from 5-HT reuptake inhibition but may be related to activation of 5-HT neurons. The potential therapeutic role of serotonergic effects in ADHD treatment merits further exploration.

Background: An ethnobotanical study showed that the leaf of Stephania abyssinica (S. abyssinica) is used for the treatment of gastritis, but there is no scientific investigation.

Objective: The aim of this study was to evaluate the gastroprotective activities of both aqueous and 80% methanol leaf extracts of S. abyssinica in experimental rats.

Methods: Decoction and maceration techniques were used to prepare aqueous and 80% methanol leaf extracts, respectively. The extracts were evaluated against pyloric ligation, indomethacin, and ethanol-induced gastric ulcer models at doses of 100, 200, and 400 mg/kg. Negative control received 2% tween 80, while positive controls received 20 mg/kg of omeprazole and 100 µg/kg of misoprostol. Parameters, such as ulcer index, gastric mucin content, gastric juice volume, pH, and free and total acidity were measured.

Results: In the pyloric ligation induced gastric ulcer model, all doses of both extracts significantly reduced the ulcer index and gastric juice volume, while doses of 200 and 400 mg/kg exhibited a significant increment in mucus content and gastric juice pH as well as decrease in free and total acidity as compared to negative control. In indomethacin and ethanol induced gastric ulcer models, pretreatment with both extracts significantly reduced the ulcer index and enhanced gastric mucin content in a dose-dependent manner. Phytochemical screening of both extracts showed the existence of flavonoids, phenols, tannins, saponins, alkaloids, and coumarins with high contents of phenols, flavonoids, and alkaloids in 80% methanol extract.

Conclusion: This study revealed that aqueous and 80% methanol leaf extracts of S. abyssinica possessed remarkable gastroprotective activities against experimentally induced gastric ulcer models, and this possibly justify the traditional use of S. abyssinica leaves to treat gastritis.

Background: Olinia rochetiana has been used traditionally to cure diarrheal disease. Therefore, this study aimed to investigate the acute toxicity and antidiarrheal effect of O. rochetiana leaf extracts.

Methods: Cold maceration was used to extract plant leaf powder with 80% methanol. The extract's antidiarrheal action was tested against a castor oil-induced diarrheal model, a charcoal meal test, and enteropooling tests at doses of 100, 200, and 400 mg/kg. Negative controls received the vehicle at 10 mL/kg, while positive controls received loperamide at 3 mg/kg.

Results: From the study, no apparent toxicity was observed when a single dose of 2000 mg/kg was administered. In the castor oil-induced model, the extract delayed the onset of diarrhea, reduced stool frequency, and decreased wet feces weight and number in a dose-dependent manner at 200 mg/kg (p < 0.05) and 400 mg/kg (p < 0.01). The percent reduction in moist feces at 100, 200, and 400 mg/kg was 54.2, 23.97, and 18.26%, respectively, indicating a significant dose-dependent decrease. In a charcoal meal test, the extracts at 200 and 400 mg/kg revealed a peristaltic index of 65 and 46%, respectively, with considerable inhibition of charcoal transport at 23 and 39%. The weight and volume of intestinal contents dropped significantly at a dose of 400 mg/kg (p < 0.01), which is 0.43 mg/kg, in the enteropooling test when compared with the tested dose. The computed in vivo antidiarrheal index revealed diarrheal inhibition values of 46.06 and 71.06% at 200 and 400 mg/kg, respectively.

Conclusion: In the current investigation, O. rochetiana showed significant antidiarrheal activity with no symptoms of toxicity in mice.

Purpose: This study evaluates the acute and sub-acute toxicity of 80% methanolic extracts of the leaves of Justicia schimperiana in Wistar albino rat models.

Methods: Dried powdered leaves of Justicia schimperiana were macerated in 80% methanol. The experiment was conducted in accordance with the Organization for Economic Co-operation and Development guideline 423 for acute and 407 for sub-acute toxicity testing. A single dose of 5000 mg/kg extract was orally administered to three female rats for the acute toxicity study. The plant extract was administered orally for 28 days in daily dosages of 250, 500, and 1000 mg/kg for the sub-acute study. Animals in a control group were given distilled water. A total of 40 rats (5 rats/group/sex) were used for the sub-acute toxicity testing. Daily food intake and weekly body weight measurements were done. The rats were sacrificed at the end of the 28-day treatment period for hematological, biochemical, and histopathological tests. One-way analysis of variance and Kruskal-Wallis tests were employed for the analysis.

Results: The single-dose oral administration of the plant resulted in no deaths or serious morbidity. The median lethal dose was >5000 mg/kg. The 28-day oral treatment of the plant extract had no significant effect on general behavior, food intake, organ weight, biochemical parameters, or the majority of the hematological markers, with the exception of the decrease in hemoglobin and hematocrit in the 1000 mg/kg extract-treated groups compared to the controls. Both sexes experienced significant weight increases at all dosage levels. With the exception of minor alterations in a few of the organs, no significant histological change was identified.

Conclusion: It is concluded that the single-dose and repeated-dose 28-day oral administration of the methanolic leaf extract of Justicia schimperiana is relatively safe.